Wang:Research
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My laboratory is primarily interested in understanding the genomic function of androgen receptor (AR) in the development and progression of prostate cancer. AR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor (NR) superfamily. Recently, we have utilized high-throughput techniques such as ChIP-exo (chromatin immunoprecipitation-exonuclease combined with high-throughput sequencing) and ChIP-seq (ChIP combined with high-throughput sequencing) to globally identify AR-bound genomic sites and precisely define AR binding motifs leading to target gene expression at various stages of prostate cancer, including androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC). By combining AR binding maps with gene expression profiles, we have begun to understand how AR regulates target gene networks in ADPC and CRPC. We are extending our view from transcriptional regulation by AR alone to include a wider view of transcription regulation in prostate cancer. These efforts have included studies of transcription factor-centered, multi-layer transcription regulatory networks in prostate cancer, which involve transcription factors (e.g. AR, FOXA1 and GATA2), transcription coactivators (e.g. Mediator and histone acetyltransferases), and epigenetic regulators (e.g. histone modifications and chromatin looping). These efforts are leading to many exciting results that will inform the development of more effective options for targeting AR activity throughout all stages of prostate cancer. Our results have also indicated that several additional, and perhaps druggable, factors play an AR-independent role in supporting prostate cancer growth at various stages of the disease. Finally, our understanding of AR genomic activity has allowed us to extend our investigations to study the genomic functions of other NRs (e.g. glucocorticoid receptor) in non-prostatic cancers, such as breast cancer. |
